Cure of prediabetic mice by viral infections involves lymphocyte recruitment along an IP-10 gradient
Cure of prediabetic mice by viral infections involves lymphocyte recruitment along an IP-10 gradient
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DOI：
10.1172/jci200417005
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发表时间：
2004-01-01
影响因子：
15.9
通讯作者：
von Herrath, MG
中科院分区：
文献类型：
--
作者：
Christen, U;Benke, D;von Herrath, MG
病毒可以引起但也可以预防自身免疫性疾病。这种二元论无疑阻碍了在病毒感染和1型糖尿病（T1 D）之间建立因果关系的尝试。为了更好地了解病毒如何影响自身免疫性疾病的发展，我们将糖尿病前期小鼠暴露于各种病毒感染。我们使用了完善的自身免疫性糖尿病NOD和转基因RIP-LCMV模型。在这两种情况下，感染淋巴细胞性脉络丛脑膜炎病毒（LCMV）完全废除糖尿病的过程。有趣的是，这种治疗性病毒感染导致T淋巴细胞从胰岛浸润物快速募集到胰腺引流淋巴结，在那里发生增加的凋亡。在这两种模型中，这与胰腺引流淋巴结中趋化因子IP-10（CXCL 10）的选择性和广泛表达相关，该趋化因子主要吸引活化的T淋巴细胞，并且在RIP-LCMV小鼠中，它依赖于病毒抗原载量。在RIP-LCMV小鼠中，体内TNF-α或IFN-γ的阻断废除了T1 D的预防。因此，如果在正确的位置、时间和水平产生，重要诱导的促炎细胞因子和趋化因子可以在临床前阶段有益地影响正在进行的自身侵袭过程。
Viruses can cause but can also prevent autoimmune disease. This dualism has certainly hampered attempts to establish a causal relationship between viral infections and type 1 diabetes (T1D). To develop a better mechanistic understanding of how viruses can influence the development of autoimmune disease, we exposed prediabetic mice to various viral infections. We used the well-established NOD and transgenic RIP-LCMV models of autoimmune diabetes. In both cases, infection with the lymphocytic choriomeningitis virus (LCMV) completely abrogated the diabetic process. Interestingly, such therapeutic viral infections resulted in a rapid recruitment of T lymphocytes from the islet infiltrate to the pancreatic draining lymph node, where increased apoptosis was occurring. In both models this was associated with a selective and extensive expression of the chemokine IP-10 (CXCL10), which predominantly attracts activated T lymphocytes, in the pancreatic draining lymph node, and in RIP-LCMV mice it depended on the viral antigenic load. In RIP-LCMV mice, blockade of TNF-alpha or IFN-gamma in vivo abolished the prevention of T1D. Thus, vitally induced proinflammatory cytokines and chemokines can influence the ongoing autoaggressive process beneficially at the preclinical stage, if produced at the correct location, time, and levels.